System and method for monitoring and determining patient parameters from sensed venous waveform

ABSTRACT

Devices, systems, and methods for monitoring patient hemodynamic status, systemic vascular resistance, reversal of cardiac and respiratory rates, and patient respiratory volume or effort are disclosed. A peripheral venous pressure is measured and used to detect levels, changes, or problems relating to patient blood volume. The peripheral venous pressure measurement is transformed from the time domain to the frequency domain for analysis. A heart rate frequency is identified, and harmonics of the heart rate frequency are detected and evaluated to determine, among other things, hypovolemia or hypervolemia, systemic vascular resistance, and of cardiac and respiratory rates, and patient respiratory volume or effort.

PRIORITY CLAIM

This application is a continuation of U.S. patent application Ser. No.16/109,252, entitled “System and Method for Monitoring and DeterminingPatient Parameters from Sensed Venous Waveform”, filed Aug. 22, 2018,which claims priority to U.S. Provisional Application No. 62/671,108,entitled “System and Method for Monitoring and Determining PatientParameters From Sensed Venous Waveform”, filed May 14, 2018, the entirecontents of which are incorporated herein by reference and relied upon.

BACKGROUND

Conventional methods of establishing blood volume and related metricsregarding patient condition have relied upon highly invasivemeasurements, such as central venous pressure (herein “CVP”), pulmonaryartery pressure, and/or capillary pressure. Such CVP measurementsrequire the insertion of a catheter, specifically for the purpose ofmeasuring blood pressure, within the central portion of the patient'scirculatory system. In addition to being highly invasive, the insertionof a catheter solely for the purpose of pressure monitoring increasesthe complexity of treatment and raises the risk of complications, suchas infection. Additionally, CVP measurements are believed to be slowerto change in response to certain acute conditions, as the circulatorysystem attempts to compensate for blood volume disequilibrium(particularly with respect to hypovolemia) by protecting blood volumelevels in the central circulatory system at the expense of theperiphery. For example, constriction in peripheral blood vessels mayreduce the effect of fluid loss on the central system, thereby maskingblood loss for a period of time in conventional CVP measurements. Suchmasking can lead to delayed recognition and treatment of patientconditions, resulting in worse patient outcomes.

To address the issues associated with CVP measurements, the use ofperipheral intravenous analysis (PIVA) has been developed, as describedin U.S. patent application Ser. No. 14/853,504 (filed Sep. 14, 2015 andpublished as U.S. Patent Publication No. 2016/0073959) and PCTApplication No. PCT/US16/16420 (filed Feb. 3, 2016, and published as WO2016/126856). Such PIVA techniques measure peripheral venous pressure(PVP) using intravenous (IV) lines, such as IV tubing which may or maynot be attached to a saline drip, infusion pump, or dialysis pump. Inaddition to utilizing existing IV lines, the PIVA techniques alsoinclude transformation of the PVP measurements into the frequency domainto identify a respiratory rate frequency (F₀) equal to the respiratoryrate of the patient and a heart rate frequency (F₁) equal to the heartrate of the patient. Although the PIVA techniques previously disclosedprovide an excellent indication of heart rate and blood volume status incertain situations, the disclosure herein further improves upon thepreviously disclosed PIVA techniques to address challenges related toother situations, improve accuracy, provide earlier warnings ofpotential problems, and identify additional patient conditions.

SUMMARY

In light of the present disclosure, and without limiting the scope ofthe disclosure in any way, in a first aspect of the present disclosure,which may be combined with any other aspect listed herein unlessspecified otherwise, a blood volume evaluation system for monitoring apatient using a measurement associated with a peripheral venous pressure(PVP) within a peripheral vein of a circulatory system of the patientincludes a PVP sensor and an evaluation unit. The PVP sensor includes atransducer disposed adjacent to or connected to an intravenous (IV) tubein fluid connection with the peripheral vein and configured to generatean electronic signal associated with the PVP. The evaluation unitincludes a computer processor communicatively connected to the PVPsensor to receive the electronic signal and a memory storingnon-transitory computer-readable instructions that, when executed by thecomputer processor, cause the evaluation unit to obtain a time-domainPVP signal, including a plurality of values of the electronic signalover a sample period. The evaluation unit then applies a transformationto the time-domain PVP signal to generate a frequency-domain PVP signal.The evaluation unit identifies a plurality of frequencies associatedwith local maxima of the frequency-domain PVP signal, including a heartrate frequency (F₁), a first harmonic frequency (F₂) at a first harmonicof the heart rate frequency, and a second harmonic frequency (F₃) at asecond harmonic of the heart rate frequency. The evaluation unitcalculates a blood volume metric based at least in part upon the heartrate frequency (F₁), the first harmonic frequency (F₂), and the secondharmonic frequency (F₃).

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, calculating theblood volume metric based at least in part upon the heart rate frequency(F₁), the first harmonic frequency (F₂), and the second harmonicfrequency (F₃) includes the equation

${{PIVA}\mspace{14mu}{Score}} = {{c_{3}{\tanh( \frac{g_{0} + {g_{1}{mag}^{f\; 1}} + {g_{2}{mag}^{f\; 2}} + {g_{3}{mag}^{f\; 3}}}{2} )}} + {c_{2}{\tanh( \frac{h_{0} + {h_{1}{mag}^{f\; 1}} + {h_{2}{mag}^{f\; 2}} + {h_{3}{mag}^{f\; 3}}}{2} )}} + {c_{1}{\tanh( \frac{i_{0} + {i_{1}{mag}^{f\; 1}} + {i_{2}{mag}^{f\; 2}} + {i_{3}{mag}^{f\; 3}}}{2} )}} + c_{0}}$

where each of c₀, c₁, c₂, c₃, g₀, g₁, g₂, g₃, h₀, h₁, h₂, h₃, i₀, i₁,i₂, and i₃ are constants. Furthermore, mag^(f1) is the magnitude of theheart rate frequency (F₁), mag^(f2) is the magnitude of the firstharmonic frequency (F₂), and mag is the magnitude of the second harmonicfrequency (F₃).

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the blood volumemetric is an indication of one of the following: hypovolemia,hypervolemia, or euvolemia.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the systemfurther includes an alarm unit configured to present alarms to a user.The instructions further cause the evaluation unit to communicate analarm indicator to a presentation unit when the blood volume metricindicates the blood volume of the patient is abnormal, the alarmindicator causing the presentation unit to present an alarm.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the alarmincludes a recommendation of an action to be taken in response to thecalculated blood volume metric.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the electronicsignal is an electronic pressure signal indicative of pressure withinthe IV tube.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the transducer ofthe PVP sensor is a pressure sensor and is disposed in fluid connectionwith the interior of the IV tube. Furthermore, the interior of the IVtube is in fluid connection with the circulatory system of the patientvia the peripheral vein.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, a device formeasuring and evaluating blood volume of a patient, includes aperipheral venous pressure (PVP) sensor and an evaluation unit. The PVPsensor includes a transducer configured to generate an electronic signalassociated with a pressure within a peripheral vein of a circulatorysystem of the patient. The evaluation unit includes a computer processorcommunicatively connected to the PVP sensor to receive the electronicsignal and a memory storing non-transitory computer-readableinstructions that, when executed by the computer processor, cause theevaluation unit to obtain a time-domain PVP signal, including aplurality of values of the electronic signal over a sample period. Theevaluation unit then applies a transformation to the time-domain PVPsignal to generate a frequency-domain PVP signal. The evaluation unitidentifies a plurality of frequencies associated with local maxima ofthe frequency-domain PVP signal, including a heart rate frequency (F₁),a first harmonic frequency (F₂) at a first harmonic of the heart ratefrequency, and a second harmonic frequency (F₃) at a second harmonic ofthe heart rate frequency. The evaluation unit calculates a blood volumemetric based at least in part upon the heart rate frequency (F₁), thefirst harmonic frequency (F₂), and the second harmonic frequency (F₃).

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the blood volumemetric is an indication of one of the following: hypovolemia,hypervolemia, or euvolemia.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, obtaining thetime-domain PVP signal includes receiving and storing the plurality ofvalues of the electronic signal over the sample period.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the sample periodis a fixed duration that is continuously updated on a rolling basis asnew values of the electronic signal are obtained.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, thetransformation is a fast Fourier transformation.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the blood volumemetric is further determined at least in part based upon at least one ormore additional harmonic frequency associated with additional harmonicsof the heart rate frequency (F₁).

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the blood volumemetric is determined based at least in part upon an increase or decreasein a magnitude of the frequency-domain PVP signal associated with thefirst harmonic frequency (F₂).

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, a method ofmeasuring and evaluating blood volume of a patient using a measurementassociated with a peripheral venous pressure (PVP) within a peripheralvein of a circulatory system of the patient includes monitoring, by atransducer of a PVP sensor, a physical phenomenon associated with thePVP within the peripheral vein of the circulatory system of the patient.The method includes generating, by the PVP sensor, an electronic signalassociated with the PVP over a sample period, the values of theelectronic signal over the sample period forming a time-domain PVPsignal. The method includes applying, by a processor of an evaluationunit, a transformation to the time-domain PVP signal to generate afrequency-domain PVP signal. The method includes identifying, by theprocessor of the evaluation unit, a plurality of frequencies associatedwith local maxima of the frequency-domain PVP signal, including a heartrate frequency (F₁), a first harmonic frequency (F₂) of the heart ratefrequency, and a second harmonic frequency (F₃) of the heart ratefrequency. The method includes calculating, by the processor of theevaluation unit, a blood volume metric based at least in part upon theheart rate frequency (F₁), the first harmonic frequency (F₂), and thesecond harmonic frequency (F₃).

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the blood volumemetric is an indication of one of the following: hypovolemia,hypervolemia, or euvolemia.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the plurality offrequencies further include one or more additional harmonic frequenciesassociated with additional harmonics of the heart rate frequency (F₁).

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the one or moreadditional harmonic frequencies are identified as the frequenciesassociated with local maxima of the frequency-domain PVP signal nearestto integer multiples of the heart rate frequency (F₁).

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the blood volumemetric is further determined at least in part based upon at least one ofthe additional harmonic frequencies.

In an aspect of the present disclosure, which may be combined with anyother aspect listed herein unless specified otherwise, the blood volumemetric is determined based at least in part upon a harmonics ratiobetween the first harmonic frequency (F₂) and the at least one of theadditional harmonic frequencies.

It is accordingly an advantage of the present disclosure to provideimproved accuracy with respect to PIVA monitoring.

It is another advantage of the present disclosure to provide a PIVAmonitoring devices, systems, and methods, which may more accuratelymonitor patient parameters.

It is yet another advantage of the present disclosure to provide a PIVAmonitoring devices, systems, and methods, which may provide earlierwarnings of potential problems with a patient.

It is still a further advantage of the present disclosure to provide aPIVA monitoring devices, systems, and methods, which may identifyadditional patient conditions.

Additional features and advantages of the disclosed devices, systems,and methods are described in, and will be apparent from, the followingDetailed Description and the Figures. The features and advantagesdescribed herein are not all-inclusive and, in particular, manyadditional features and advantages will be apparent to one of ordinaryskill in the art in view of the figures and description. Also, anyparticular embodiment does not have to have all of the advantages listedherein. Moreover, it should be noted that the language used in thespecification has been principally selected for readability andinstructional purposes, and not to limit the scope of the inventivesubject matter.

BRIEF DESCRIPTION OF THE FIGURES

Understanding that the figures depict only typical embodiments and arenot to be considered to be limiting the scope of the present disclosure,the present disclosure is described and explained with additionalspecificity and detail through the use of the accompanying figures. Thefigures are listed below.

FIG. 1 illustrates a block diagram of an exemplary PIVA system for usein measuring, analyzing, and responding to a patient's peripheral venousblood pressure, according to an example embodiment of the presentdisclosure.

FIG. 2 illustrates a block diagram of an exemplary PIVA device forimplementing some functions of the exemplary PIVA system, according toan example embodiment of the present disclosure.

FIG. 3 illustrates a flow diagram of an exemplary PIVA measurement andanalysis method for measuring and analyzing a patient's peripheralvenous blood pressure, according to an example embodiment of the presentdisclosure.

FIG. 4A illustrates an exemplary plot of time-domain representation of aperipheral venous pressure signal, according to an example embodiment ofthe present disclosure.

FIG. 4B illustrates an exemplary plot of frequency-domain representationof a peripheral venous pressure signal, according to an exampleembodiment of the present disclosure.

FIG. 4C illustrates an exemplary plot of frequency-domain representationof a peripheral venous pressure signal, according to an exampleembodiment of the present disclosure.

FIG. 5 illustrates an exemplary PIVA comparison method for identifyingchanges in a patient status based upon comparison of peripheral venouspressure over time, according to an example embodiment of the presentdisclosure.

FIG. 6 illustrates a block diagram of an exemplary PIVA system for usein measuring, analyzing, and responding to a patient's peripheral venousblood pressure, according to an example embodiment of the presentdisclosure.

DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS

FIG. 1 illustrates a block diagram of an exemplary PIVA system 100 foruse in measuring, analyzing, and responding to peripheral venous bloodpressure of a patient 102. The exemplary PIVA system 100 or a similarsystem may be used to implement the various techniques for monitoringpatient status based upon measurements associated with PVP for thepatient 102. The PIVA system 100 may measure a pressure signalassociated with the patient's peripheral vein, analyze the pressureusing PIVA techniques to identify key frequency components of thepressure signal, and analyze the key frequency components of thepressure signal to determine patient status based upon one or moremetrics, as discussed below.

The PIVA system 100 includes an IV tube 104 in fluid connection with thecirculatory system of the patient 102. Specifically, a venous accessdevice 106 may be inserted into a peripheral vein 108 of the patient 102at an access point. The venous access device 106 may include a needle,catheter, cannula, or other means of establishing a fluid connectionbetween the IV tube 104 and the peripheral vein 108. The venous accessdevice 106 may be a separate component connected to the IV tube 104 ormay be formed as an integral portion of the IV tube 104. In either case,the venous access device 106 may include a terminal end inserted intothe peripheral vein 108 at the access point and a connecting end thatconnects to a primary portion of the IV tube 104. The primary portion ofthe IV tube 104 may serve as a conduit between the venous access device106 and a fluid source 110.

At some point along the primary portion of the IV tube 104, a pressuresensor 112 may be disposed in fluid connection with the interior of theIV tube 104. The pressure sensor 112 is thus also in fluid connectionwith the peripheral vein 108 of the patient through the IV tube 104 andthe venous access device 106. The pressure sensor 112 is thereby enabledto measure pressure changes in the peripheral venous system of thepatient 102 based upon changes in the fluid pressure within the IV tube104. In other embodiments, the pressure sensor 112 may not be disposedin fluid connection with the interior of the IV tube 104. For example,the pressure sensor 112 may instead be attached to the exterior of theIV tube 104 and thereby not directly in fluid communication with thefluid source 110. The pressure sensor 112 may, in some such embodiments,measure pressure based upon acoustic or optical phenomenon at the sensorlocation. In some embodiments, the pressure sensor 112 may be disposedat a terminating end (i.e., a capped off end) of an IV tube 104 insertedspecifically for the purpose of measuring pressure within the peripheralvein 108, in a manner similar to the device illustrated below in FIG. 2.In still other embodiments, other sensors may be used instead of thepressure sensor 112, such as force sensors, sound sensors, and sensorsthat need not be in fluid contact with the peripheral vein 108 of thepatient through the IV tube 104 and the venous access device 106. In yetfurther embodiments, the sensor 112 may be disposed within a portion ofa needle, catheter, or other venous access device 106 that is insertedwithin the peripheral vein 108 of the patient 106, such that PVP may bemeasured in situ within the peripheral vein 108. Such in situmeasurement is advantageous inasmuch as it obviates the effect oftemperature, viscosity, and other factors on transmission of pressurewithin the IV tube 104.

In various embodiments, the pressure sensor 112 may be positioned atvarious distances from the access point of the peripheral vein 108, froma location within the peripheral vein 108 or a location proximate to theconnecting end of the venous access device 106 to a position proximateto the fluid source 110 or at a terminating end of the IV tube 104. Thepressure sensor 112 is shown in FIG. 1 as being at an intermediatelocation along the length of the IV tube 104, in order to betterillustrate the various components of the PIVA system 100. In someembodiments, the pressure sensor 112 may directly measure fluid pressurewithin the IV tube 104. Specifically, the pressure sensor 112 mayinclude a transducer that provides an electronic pressure signalindicative of the pressure detected by the transducer to an analysiscomponent 114 via a connection 122. The electronic pressure signal maybe an analog electrical signal directly provided by the transducer ormay be a preprocessed digital signal indicating pressure values basedupon the transducer interface with the primary portion of the IV tube104. In embodiments in which the pressure sensor 112 is not in fluidconnection with the IV tube 104 or the peripheral vein 108, the pressuresensor 112 may nonetheless include one or more transducers to generateelectronic signals associated with the PVP. For example, the pressuresensor 112 may use one or more microphones disposed to detect sound atan exterior surface of an IV tube 104 to generate electronic pressuresignals indicative of pressure within the IV tube 104 as a proxy for PVPwithin the peripheral vein 108.

The analysis component 114 is communicatively connected to the pressuresensor 112 to receive the electronic pressure signal via the connection122. The analysis component 114 may include general-purpose orspecial-purpose processing hardware, such as microprocessors orspecial-purpose analysis circuits. As shown, the analysis component 114may include one or more units for performing the PIVA analysis. Aresponse unit 116 may identify and control responses based upon thepressure data from the pressure sensor 112. The response unit 116 maycontrol the presentation of alarms, such as visual alarms (e.g., viamonitor 120) and audible alarms (e.g., via a speaker in communicationwith the PIVA system 100). Likewise, the response unit 116 may controlthe operation of the fluid source 110, such as by controlling the rateof fluid flow. To determine appropriate responses, the response unit 116may receive evaluation data from an evaluation unit 118, which mayinclude metrics determined from the electronic pressure signal. Theevaluation unit 118 may obtain pressure values (or signal valuesdirectly or indirectly associated with PVP) from the electronic pressuresignal and evaluate the pressure values to determine informationregarding the patient 102, such as blood volume metrics or other metricsas described in further detail below. The information generated by theevaluation unit 118 may also be stored or presented for patientmonitoring (e.g., via monitor 120). In alternative embodiments,additional, fewer, or alternative units may be included. For example,the evaluation unit 118 may perform the functions ascribed to theresponse unit 116 herein.

The analysis component 114 may be communicatively connected to a monitor120 via a connection 126 in some embodiments. The monitor 120 may be aseparate monitor for displaying information regarding the patient or maybe incorporated into another device, such as a pump or other fluidsource device. The monitor 120 may also be communicatively connected tothe fluid source 110 via a connection 128 to receive and displayinformation associated with the fluid source 110. In some embodiments,the monitor 120 may be used to control the operation of the fluid source110, such as by adjusting fluid flow rate, duration of operation, modeof operation, etc. The analysis component 114 may similarly becommunicatively connected to the fluid source 110 via connection 124 insome embodiments. The analysis component 114 may receive informationregarding operation of the fluid source 110 for use in evaluating thepatient by the evaluation unit 118. The response unit 116 may alsocommunicate with the fluid source 110 to control operation of the fluidsource 110 in response to information regarding the patient determinedbased upon the electronic pressure signal from the pressure sensor 112.

The various connections 122, 124, 126, and 128 may each be wired orwireless connections in various embodiments. Moreover, some or all ofthe connections 122, 124, 126, and 128 may be internal to devices, suchas a PIVA device 130 or a PIVA-integrated fluid source 140.

The PIVA device 130 may incorporate the pressure sensor 112 and analysiscomponent 114 (along with associated connections) into a device that maybe attached to or within the IV tube 104 to perform PIVA monitoring ofthe patient 102. The PIVA-integrated fluid source 140 may include acomputer-controlled fluid reservoir or pump configured to utilize PIVAmonitoring of the patient 102 in controlling fluid flow. Like the PIVAdevice 130, the PIVA-integrated fluid source 140 may include thepressure sensor 112 and analysis component 114, along with the fluidsource 110 and the monitor 120 (along with associated connections).Alternative embodiments may include additional, fewer, or alternativecomponents in alternative configurations.

FIG. 2 illustrates a block diagram of an exemplary PIVA device 130 forimplementing some functions of the exemplary PIVA system 100. Asillustrated, the exemplary PIVA device 130 may be configured to attachto a spur 104A of the IV tube 104, such as at one branch of aY-connector or a T-connector. As above, the PIVA device 130 may includea pressure sensor 112 disposed such that a sensing portion is in contactwith fluid in the IV tube 104 (illustrated as the IV tube spur 104A).The pressure sensor 112 may be electrically communicatively connected toa microprocessor 132 via a system bus 138. The microprocessor 132 (MP)may be further communicatively connected to a program memory 134 and acommunication unit 136 (COMM UNIT) via the system bus 138. The programmemory 134 may be a non-transitory, non-volatile memory (e.g., a flashmemory) storing executable instructions that may be executed by themicroprocessor 132 to evaluate the electronic pressure signal from thepressure sensor 112, determine patient information (e.g., blood volumemetrics and/or respiratory metrics), determine appropriate responses tothe determined patient information, and control the communication unit136 to electronically communicate with the fluid source 110 or monitor120 via connections 124 or 126. The program memory 134 may store aplurality of routines, scripts, or modules corresponding to units orsub-units of the analysis component 114. The communication unit 136 maybe a hardware component configured to send and receive electronic databetween the PIVA device 130 and the fluid source 110 or monitor 120 viaconnections 124 or 126. The connections 124 and 126 are illustrated asbeing wired connections in the exemplary PIVA device 130, which may alsobe used to obtain power for the PIVA device 130. Alternatively, anotherpower connection or battery (not shown) may provide power to the PIVAdevice 130.

Although the PIVA device 130 is illustrated as being connected to a spur140A of the IV tube 104, some embodiments may include an IV tube 104terminating at the spur 104A, without another branch or portion of theIV tube 104 that connects to a fluid source 110. In such embodiments,the entire IV tube 104 may consist of the spur 104A as a non-branchingtube, which may directly connect to or incorporate the venous accessdevice 106. Thus, the PIVA device 130 may cap a terminating portion ofsuch an IV tube 104/104A, such that no fluid source 110 is connected tothe peripheral vein 108 through the same IV tube 104/104A and venousaccess device 106. In this embodiment, a fluid source could be otherwiseconnected to provide fluids to the patient 102 via another IV tube andanother venous access device.

FIG. 3 illustrates a flow diagram of an exemplary PIVA measurement andanalysis method 300 for measuring and analyzing a status of a patient102 based on PVP using the PIVA system 100. The method 300 may be usedto determine various patient status metrics, such as metrics related topatient blood pressure, blood volume, respiration, respiratory volume,respiratory effort, or systemic vascular resistance. The method 300 maybe performed by the evaluation unit 118 using an electronic pressuresignal from the pressure sensor 112, the generation of which electronicpressure signal by the pressure sensor 112 may be included in the method300 in some embodiments.

The method 300 begins with measuring a PVP data signal for the patient102 (block 302). The PVP data signal may be measured by using atransducer of the pressure sensor 112 to generate an electronic pressuresignal associated with the pressure within the IV tube 104. Because theIV tube 104 is in fluid connection with the peripheral vein 108 of thepatient 102 via the venous access device 106, the pressure in the IVtube 104 measured by the pressure sensor 112 is associated with thepressure in the peripheral vein 108. In some embodiments of the PIVAsystem 100, the pressure within the IV tube 104 may be different fromthe PVP within the peripheral vein 108, but the pressure measured withinthe IV tube 104 may nonetheless be proportional to, or otherwise relatedto, the PVP in the peripheral vein 108. Thus, the measured PVP datasignal may be adjusted to compensate for differences between thepressures, if desired. For example, adjustments may be made based upontemperature, viscosity of the patient's blood or a fluid provided by thefluid source 110, or a gauge or rigidity of the IV tube 104, or othersystem variation that may impact the PIVA signal. Whether adjusted orunadjusted, the PVP data signal measured by the pressure sensor 112accurately represents changes in pressure over time, including bothperiodic pressure changes associated with respiratory and circulatorycycles and aperiodic pressure changes that may be indicative of changesin patient condition. Similarly, a PVP data signal generated by thepressure sensor 112 by components not in fluid contact with the interiorof the IV tube 104, likewise, provides a representation of the pressurewithin the peripheral vein 108 of the patient 102. The PVP data signalmay be the electronic pressure signal generated by the pressure sensor112 or may be a data signal derived therefrom. In alternativeembodiments, the PVP data signal may be evaluated in real-time as it isgenerated, or it may be stored for later analysis.

FIG. 4A illustrates an exemplary chart of a time-domain representationof the PVP data signal, which may be the electronic pressure signal fromthe pressure sensor 112. The chart illustrates a time-domain PVP signal402, which shows periodic increases and decreases in pressure associatedwith the patient heartbeat. Additionally, the time-domain PVP signal 402exhibits slower cyclical variation as a result of, for example, patientrespiration. The chart also illustrates a respiration curve 404 thatshows the effect of inspiration and expiration on the time-domain PVPsignal 402. For example, because of the expansion of the lungs duringinspiration, the baseline measured venous blood pressure is higherduring inspiration than during expiration, when the volume of the lungsis reduced due to the expansion of the diaphragm pressing against theflexible vena cava (and other large veins) in the abdominal cavityand/or by increasing the peripheral venous flows toward the heart. Onthe other hand, expiration relieves the pressure caused by the diaphragmproximation against the vena cava. Many other factors influence PVP,such as blood volume and patient movement.

The time-domain PVP signal 402 is thus a combination of a plurality ofinfluences, both periodic (e.g., heart rate or respiration) andaperiodic (e.g., movement or blood loss). Because the resultingtime-domain PVP signal 402 will include noise from various sources, itmay be difficult to detect small changes in pressure that may serve asindications of patient status. Therefore, PIVA techniques utilize afrequency-domain evaluation of the PVP data signal, as described below.It should be recognized that, although the time-domain representation ofthe PVP data signal is illustrated graphically as a chart in FIG. 4A toillustrate the salient features of the data, it is not necessary toproduce a chart or other graphical representation of such data signal.Instead, in certain embodiments, the PVP data signal is processed by theevaluation unit 118 without generating a graphical representation of thetime-domain PVP data signal.

Returning to FIG. 3, a plurality of data values may then be obtainedfrom the measured PVP data signal (block 304). The evaluation unit 118may sample values of the live or stored PVP data signal to obtain theplurality of data values. In some embodiments, the data values may besampled at fixed intervals over a period of time to obtain a pluralityof data values within an evaluation window, which may include storingthe plurality of data values associated with the window in temporary orpermanent electronic data storage. In further embodiments, data formultiple evaluation windows may be obtained, such that each evaluationwindow includes a plurality of data values. For example, concurrent timeperiods may be identified as separate evaluation windows, or evaluationwindows may be identified as time periods separated by an interveningperiod (e.g., twenty-second evaluation windows beginning every minute,thus separated by forty-second intervening periods). When the evaluationunit 118 samples values of a live (continuously updating) PVP datasignal, in some embodiments, the evaluation window may be updated on arolling basis to obtain new data values while covering time periods offixed duration. For example, the evaluation window may be repeatedlyupdated by adding new sample data values and removing the oldest sampledata values to maintain a window of a fixed duration (e.g., fiveseconds, ten seconds, twenty seconds, etc.) of the most recent PVP datafrom the pressure sensor 112. Where the evaluation unit 118 periodicallyobtains updates of new sample data values, the window may be updated(and the transformation and evaluation described below may be performedfor the updated window) every time a new data value is received. In analternative embodiment, the plurality of data values may correspond tothe continuous values of an analog PVP data signal, which may beobtained and analyzed by analog electronic equipment (which may be partof the evaluation unit 118).

From the plurality of data values, the evaluation unit 118 generatesfrequency-domain data corresponding to the plurality of data values(block 306). This may include applying a data transformation to theplurality of data values representing a time-domain PVP signal toproduce a frequency-domain representation of the PVP signal. In apreferred embodiment, the evaluation unit 118 applies a fast Fouriertransform (FFT) to the sampled plurality of data values. The FFT may beapplied periodically (e.g., every ten seconds, every minute, or everytwo seconds, with or without overlapping evaluation windows). Otheranalysis techniques that can separate frequencies and identify localmaxima according to frequency are contemplated, such as wavelettransform.

The frequency-domain data may include a plurality of values representingthe magnitude of various frequency components in the measured PVP datasignal based upon the plurality of data values. Such values may bediscrete or may be part of a curve of magnitudes corresponding tofrequencies, which curve may be generated by interpolation orapproximation between a finite number of values associated with a finitenumber of frequencies. Although FFT algorithms may be used to greateffect, other time-frequency transforms or other techniques of analyzingfrequency components of signals may be utilized to evaluate theplurality of data values. For example, in addition to other Fouriertransforms, the evaluation may include wavelet transforms ortime-frequency representations of the measured PVP data signal.

FIG. 4B illustrates an exemplary chart of a frequency-domainrepresentation of the PVP data signal, corresponding to the time-domainPVP signal 402 represented in the time domain in FIG. 4A. The chartillustrates the magnitude of each frequency component by a frequencycurve 406. Because the chart in FIG. 4B is a frequency-domainrepresentation, the horizontal axis represents frequency, and thevertical axis represents magnitude. Although the chart is exemplary,certain typical features may be discerned therein. Of particularinterest are the several peaks (P_(N)) of the frequency curve 406associated with frequencies (F_(N)). Between the peaks, minor variationsin magnitude are seen, which may represent minor components of thetime-domain PVP signal 402 associated with noise in the system orartifacts of the circulatory system (e.g., movements of the patientduring measurement, openings and closings of the atrioventricular andaortic valves, etc.). In certain embodiments, the frequency domainrepresentation generated by PIVA system 100 is displayed (e.g., viamonitor 120).

Although the frequency-domain representation of the PVP data signal isillustrated in FIG. 4B as a chart to illustrate the salient features, itshould be understood that it is not necessary to produce a chart orother graphical representation of the frequency-domain data. Indeed, incertain embodiments, no such graphical representation is generated.Instead, the frequency-domain data is processed by the evaluation unit118 as an intermediate process, the results of which are not directlypresented to a user of the system or device.

Under ordinary conditions, the peak (P₀) with the lowest frequency (F₀)corresponds to the respiration rate of the patient 102, and the peak(P₁) with the next-lowest frequency (F₁) corresponds to the heart rateof the patient 102. One or more harmonic peaks (P_(H)) associated withharmonic frequencies (F_(H)) of the heart rate frequency (F₁) may beidentified in some embodiments. Such harmonic peaks (P_(H)) areassociated with local maxima of the frequency curve 406. For example,the next two peaks (P₂) and (P₃) of the frequency curve 406 are harmonicpeaks (P_(H)) occurring at frequencies associated with the first andsecond harmonics of the heart rate at the first harmonic frequency (F₂)and the second harmonic frequency (F₃) respectively. The identifiedharmonics occur at fixed multiples of the heart rate frequency (F₁).Typically, these multiples are integer multiples. Specifically,experimental data indicate that first harmonic frequency (F₂) isapproximately twice the heart rate frequency (F₁), and the secondharmonic frequency (F₃) is approximately thrice the heart rate frequency(F₁), as illustrated by FIG. 4B.

Identification of the peaks (e.g., P₁, P₂, P₃) of the correspondingfrequencies (e.g., F₁, F₂, F₃), such as via the evaluation unit 118,provides for subsequent calculations of patient status (e.g.,hemodynamic status). For example, the peaks (e.g., P₁, P₂, P₃) of thecorresponding frequencies (e.g., F₁, F₂, F₃) may be used to calculate aPIVA Score, as further detailed herein.

Although not shown, additional peaks associated with third and higherharmonics of the heart rate may be identified in some embodiments. Thefurther harmonic frequencies (F₄, F₅, . . . F_(N)) typically occur atcorresponding sequential integer multiples of the heart rate frequency(F₁). For example, a second harmonic frequency may be represented by F₃,a third harmonic frequency may be represented by F₄, etc. Although somevariation exists in the observed frequencies of the peaks associatedwith the harmonic frequencies, the harmonic frequency peaks have beenfound to occur at frequencies within a range of ten percent (i.e., ±10%)of the value of the heart rate frequency above or below the integermultiples of the heart rate frequency (F₁). The relationships betweenthe magnitudes of the peaks (P_(N)) may vary, but typically themagnitude of the peak (P₁) associated with the heart rate frequency (F₁)should be greater than the magnitudes of the peaks (P₂), (P₃), etc.,associated with the harmonic frequencies (F₂), (F₃), etc., thereof.

Furthermore, it should be noted that while FIG. 4B illustrates thefrequency curve 406 as a number of parabolic peaks (e.g., P₀, P₁, P₂,P₃), other graphical representations of the frequency-domainrepresentation should be expected. For example, to the extent that thesystem is consistent (e.g., consistent patient respiration and heartrate), and the sampling rate is high enough (e.g., the sampling rate ofdata values measured in the time domain), the peaks (e.g., P₀, P₁, P₂,P₃) may be depicted graphically as vertical lines (e.g., parabolic peakswith unperceivable width or parabolic peaks with no width).

Although the present disclosure generally refers to the respiration rateas corresponding to the lowest-frequency peak (P₀), the heart rate ascorresponding to the next-lowest frequency peak (P₁), and so on, itshould be appreciated that any such reference is done for ease ofexplanation. To this end, in some embodiments, the time-domain PVPsignal may detect one or more frequencies lower than the respirationrate. For instance, gut frequencies tend to be associated with lowerfrequencies than a typical respiratory frequency. In these embodiments,the peak (P₀) with the lowest frequency (F₀) corresponds to a gutfrequency, and the peak (P₁) with the second-lowest frequency (F₁)corresponds to the respiratory frequency. Similarly, the heart ratefrequency and each of the corresponding harmonic frequencies wouldcorrespond to the next-lowest peak (P₂) and the following peaks (P₃, P₄,. . . P_(N)), respectively. It should be appreciated that in somefurther embodiments, the time-domain PVP signal may detect multiplefrequencies lower than the respiratory frequency. Accordingly, the peakindex corresponding to the respiration rate, the heart rate, and theheart rate harmonics may increase by the number of frequencies detectedlower than the respiration rate. As such, unless specifically describedotherwise, any reference to the respiratory rate corresponding to thelowest frequency peak (P₀) and the heart rate frequency corresponding tothe next-lowest frequency peak (P₁) is not limiting and also envisionsoffsetting the correspond peak indexes by the number oflower-than-respiration rate frequencies detected by the time-domain PVPsignal.

Turning again to FIG. 3, the evaluation unit 118 further identifies aplurality of peaks (P_(N)) corresponding to frequencies (F_(N)) of thefrequency-domain representation of the PVP signal (block 308), such asthe frequency curve 406. The evaluation unit 118 may first identifyvalues indicating peaks (P_(N)) in the frequency-domain representationof the PVP signal by comparison of the frequency-domain PVP signalvalues, then identify the corresponding frequencies (F_(N)) associatedwith the identified peak values (P_(N)). To determine the peak values(P_(N)), the evaluation unit 118 may utilize any of various methods toidentify local maxima as peaks, including methods based upon any or allof a comparison of the relative magnitudes of local maxima,establishment of fixed or dynamic frequency bands around each peak, orcomparison of full width at half maximum for local maxima. For example,a band-pass filter may be employed to separate segments of thefrequency-domain representation of the PVP signal to further identifylocal maxima. This may be particularly useful in identifying harmonicpeaks (P_(N)) and corresponding harmonic frequencies (F_(H)) becausesuch harmonics occur at integer multiples of the heart rate frequency(F₁).

As an example, a band-pass filter centered around a frequency twice theheart rate frequency (F₁) and having a band width of twenty percent ofthe heart rate frequency (F₁) may be used to define a range of thefrequency-domain representation of the PVP signal that contains thefirst harmonic peak (P₂). The first harmonic frequency (F₂) may then beidentified by simply determining the frequency associated with the localmaximum value of the frequency-domain representation of the PVP signalwithin such range. By employing these or other techniques, the peaks(P_(N)) of the frequency-domain representation of the PVP signal may bedistinguished from other local maxima arising from noise or other minorphenomena in the circulatory system.

Once the plurality of peaks (P_(N)) associated with the frequencies(F_(N)) have been identified, the evaluation unit 118 may analyze themagnitudes of the frequency-domain representation of the PVP signal atone or more of the frequencies (F_(N)) to determine one or more aspectsof patient status (block 310). Such analysis may include determining oneor more patient status metrics, such as a blood volume metric,respiratory volume metric, respiratory effort metric, systemic vascularresistance metric, other metric relating to the systemic vascularresistance (e.g., mean arterial pressure, mean venous pressure, cardiacoutput), or the like for the patient 102. For example, the patientstatus metrics may include a blood volume metric indicating one of thefollowing hemodynamic states of the patient 102: hypovolemia,hypervolemia, or euvolemia. In certain embodiments, hemodynamic statesof the patient 102 may be determined as a score or as a category ofpatient status.

Some patient status metrics may be determined directly from the one ormore frequencies (F_(N)) or magnitudes of the frequency-domainrepresentation of the PVP signal associated therewith. For example,respiratory rate may be determined based upon the respiratory frequency(F₀). Likewise, for example, respiratory depth may be determined basedupon the magnitude associated with the respiratory frequency (F₀) (i.e.,the magnitude of the respiratory peak (P₀)), or a blood volume metricmay be determined based upon the magnitude associated with the heartrate frequency (F₁) (i.e., the magnitude of the heart rate peak (P₁)).As another example, a blood volume metric indicative of patienthemodynamic state (e.g., hypovolemia or hypervolemia) may be directlymeasured or calculated.

For example, as previously mentioned, subsequent to performingtransformation, the evaluation unit 118 may identify the peaks (e.g.,P₁, P_(2,) P₃) of the corresponding frequencies (e.g., F₁, F₂, F₃).These individual peaks (e.g., P₁, P_(2,) P₃) corresponding to thevarious frequencies, such as the heart rate frequency F₁, the firstharmonic of the heart rate frequency F₂, and the second harmonic of theheart rate frequency F₃ may then be used in an equation to calculate aPIVA Score. PIVA Score, representative of a patient's fluid status, isalso a corollary for pulmonary capillary wedge pressure. Becausepulmonary capillary wedge pressure is an indicator of fluid status(e.g., hypervolemia or hypovolemia), the PIVA Score, likewise, isrepresentative of a patient's fluid status.

In an embodiment, the equation to calculate PIVA Score is represented bythe following:

${{PIVA}\mspace{14mu}{Score}} = {{c_{3}{\tanh( \frac{g_{0} + {g_{1}{mag}^{f\; 1}} + {g_{2}{mag}^{f\; 2}} + {g_{3}{mag}^{f\; 3}}}{2} )}} + {c_{2}{\tanh( \frac{h_{0} + {h_{1}{mag}^{f\; 1}} + {h_{2}{mag}^{f\; 2}} + {h_{3}{mag}^{f\; 3}}}{2} )}} + {c_{1}{\tanh( \frac{i_{0} + {i_{1}{mag}^{f\; 1}} + {i_{2}{mag}^{f\; 2}} + {i_{3}{mag}^{f\; 3}}}{2} )}} + c_{0}}$

Each of c₀, c₁, c₂, c₃, g₀, g₁, g₂, g₃, h₀, h₁, h₂, h₃, i₀, i₁, i₂, andi₃ are constants. Each of mag^(f1), mag^(f2), and mag^(f3) representsthe individual magnitudes of each of the respective frequencies (e.g.,F₁, F₂, F₃). These magnitudes are also commonly referred to herein aspeaks of frequencies. For example, mag may also be referred to as peakP₁ herein, associated with heart rate frequency F₁. Similarly, forexample, mag^(f2) may also be referred to as peak P₂ herein, associatedwith first harmonic frequency F₂. Similarly, for example, mag^(f3) mayalso be referred to as peak P₃ herein, associated with second harmonicfrequency F₃. For example, and with reference to FIG. 4B, P₁, referredto in the PIVA Equation as mag^(f1), is the magnitude of the heart ratefrequency (F₁), P₂, referred to in the PIVA Equation as mag^(f2), is themagnitude of a first harmonic frequency (F₂), and P₃, referred to in thePIVA Equation as mag^(f3), is the magnitude of a first harmonicfrequency (F₃)

Evaluation unit 118 calculates the PIVA score, which is unitless. In arelated embodiment, PIVA system 100 displays the PIVA score (e.g., viamonitor 120). By calculating PIVA score, a patient's fluid status may bereadily determined (e.g., hypovolemia, hypervolemia, or euvolemia).Preferably, the calculated PIVA score has an agreement with pulmonarycapillary wedge pressure of ±8 mmHg with limits of agreement of 95%confidence interval.

In an embodiment, additional peak magnitudes corresponding to variousfrequencies (e.g., P₄ corresponding to F₄, a third harmonic frequency)may also be used in calculating the PIVA score (e.g., implementingadditional constants as well) for greater accuracy in calculation.

FIG. 5 illustrates an exemplary PIVA comparison method 500 foridentifying changes in a patient status based upon comparison offrequency-domain representations of PVP signals associated withdifferent times. The PIVA comparison method 500 may be implemented bythe evaluation unit 118 and the response unit 116 to determine andrespond to changes in patient status between time periods. For example,the evaluation unit 118 may determine and compare frequency-domainrepresentations of PVP based upon electronic pressure signals receivedduring multiple time periods to determine changes in patient metrics,such as blood pressure, blood volume, respiratory volume, respiratoryeffort, or systemic vascular resistance. Specifically, the evaluationunit 118 may compare relative or absolute magnitudes associated withfrequencies (F_(N)) of peaks (P_(N)) in the frequency distributionsdetermined for each time period to identify changes in patient statusthat may be used by the response unit 118 to determine and implementresponse actions.

The exemplary method 500 begins by obtaining a first frequencydistribution associated with a first time period (block 502) and asecond frequency distribution associated with a second time period(block 504). Each of the first and second frequency distributions may begenerated as the frequency-domain data corresponding to the plurality ofdata values from the PVP data signal by the method 300, as describedabove. The first and second time periods may correspond to first andsecond evaluation windows, as discussed above, each evaluation windowbeing associated with a plurality of data values sampled or received bythe evaluation unit 118. The data values for each of the first andsecond evaluation windows may be stored in a volatile or non-volatilememory until needed by the evaluation unit 118 to generate the frequencydistributions, as discussed above. Alternatively, the frequencydistributions or information associated therewith (e.g., frequency peaksand associated magnitudes) may be stored directly for comparison. Insome embodiments, the first and second frequency distributions may befrequency-domain representation of the PVP signals from the sensor 112for time periods of fixed duration beginning at times separated by apredetermined interval. For example, the method 500 may be implementedon a rolling basis (i.e., periodically or when new PVP data becomesavailable) during real-time monitoring of the patient 102 by comparingthe magnitudes of frequency peaks (F_(N)) of frequency distributionsgenerated for first and second evaluation windows during patientmonitoring. The first and second periods may be partially overlapping,adjacent in time, or separated by an intervening period.

The evaluation unit 118 may next identify one or more peaks of interestfor determining the patient status (block 506). In a related embodiment,the evaluation unit 118 receives an indication of one or more peaks ofinterest (e.g., a user request for a peak of interest). In oneembodiment, the evaluation unit 118 may receive the indication from aninput device (e.g., a keyboard or a touchscreen), a portable electronicdevice (e.g., a mobile phone or a tablet), the PIVA device 130, or anon-PIVA circulatory pressure monitoring device.

The peaks of interest may be identified in either one or both of thefirst and second frequency distributions. In some instances, the one ormore peaks of interest may be determined based upon peaks (P_(N)) in abaseline frequency distribution generated for the patient 102, which maybe the first frequency distribution or an additional prior frequencydistribution. The baseline frequency distribution may, for example, bedetermined prior to scheduled surgery to establish a baseline for laterpatient status monitoring. The peaks of interest may be identified basedupon the associated frequencies (F_(N)), such as by identifying therespiratory frequency (F₀) or the heart rate frequency (F₁). In someembodiments, the peaks of interests may include a plurality of suchpeaks, such as the peaks (P₂) and (P₃) associated with the firstharmonic frequency (F₂) and the second harmonic frequency (F₃). Undersome conditions, not all peaks of interest may be identifiable in bothfrequency distributions. For example, during an acute failure of thecirculatory system, systemic vascular resistance may markedly decreaseand peaks associated with the harmonic frequencies (F₂, F₃, . . . F_(N))may not be discernible. Thus, the peaks associated with the harmonicfrequencies (F₂, F₃, . . . F_(N)) may be identifiable in the firstfrequency distribution but not in the second frequency distribution.Nonetheless, a change in magnitude of the frequency distributions at theharmonic frequencies (F₂, F₃, . . . F_(N)) may be determined bycomparison of the first and second frequency distributions.

Based upon the identified one or more peaks of interest, the evaluationunit 118 may further determine a patient status (or a change in patientstatus) by a comparison of the first and second frequency distributions(block 508). Determining the patient status may include a comparison ofthe magnitudes associated with the same one or more frequencies (F_(N))between the first and second frequency distributions, a comparison ofthe values of a function of a plurality of magnitudes associated withfrequencies between the first and second frequency distributions (e.g.,a comparison of ratios of peak magnitudes), a comparison of frequencies(F_(N)) associated with one or more peaks (P_(N)) between the first andsecond frequency distributions (e.g., a change in the respiratoryfrequency or heart rate frequency), or a comparison of other metricsassociated with patient status. In some embodiments, the patient statusmay be determined based upon a change in a metric beyond a thresholdlevel. For example, a decrease in the magnitude associated with theheart rate frequency (F₁) in the second frequency distribution below 80%of the corresponding magnitude associated with the heart rate frequency(F₁) in the first frequency distribution may indicate hypovolemia in thepatient 102. As another example, a decrease in the ratio of themagnitude associated with the first harmonic frequency (F₂) to themagnitude associated with the heart rate frequency (F₁) between thefirst and second frequency distributions beyond a predeterminedthreshold may indicate hypervolemia or hypovolemia, depending uponwhether and how the magnitude associated with the heart rate frequency(F₁) changes. Comparisons of particular interest are discussed infurther detail elsewhere herein.

A comparison involving one or more of the harmonic frequencies (F₂, F₃,etc.) is of particular interest regarding patient hemodynamic state orblood volume. Because the frequency distribution values associated withharmonic frequencies (F₂, F₃, etc.) are more sensitive to changes inblood volume than the values associated with the heart rate frequency(F₁), monitoring changes in the values associated with harmonicfrequencies (F₂, F₃, etc.) may provide an earlier or clearer indicationof patient hemodynamic state. For example, a sharp increase or decreasein the magnitude of the value of the frequency distribution associatedwith the first harmonic frequency (F₂) (or other harmonic frequency,such as the second harmonic frequency F₃) may be more pronounced thanthe corresponding change in the values associated with the heart ratefrequency (F₁) in the same patient at the same time. In one embodiment,comparison of an increase or decrease associated with the first harmonicfrequency (F₂) involves comparison of two separately calculated PIVAscores, such that changes to both the heart rate frequency (F₁) and thefirst harmonic frequency (F₂) are included (e.g., included via the PIVAscore equation above).

Thus, blood volume metrics may be generated using the harmonicfrequencies (F₂, F₃, etc.). Such metrics may be determined as functionsof the harmonic frequencies (F₂, F₃, etc.), ratios of the frequencyvalues of the harmonic frequencies (F₂, F₃, etc.), magnitudes associatedwith the harmonic frequencies (F₂, F₃, etc.), ratios of the magnitudesassociated with the harmonic frequencies (F₂, F₃, etc.), or changes inany of these. Such changes may be measured against a baseline or againsta previously determined value at a fixed interval in time prior to thecurrent values. In some embodiments, the frequencies or magnitudesassociated with the harmonic frequencies (F₂, F₃, etc.) may be comparedagainst other relevant values, such as frequencies or magnitudesassociated with the respiratory rate frequency (F₀) or the heart ratefrequency (F₁). For example, one or more harmonic frequencies (F₂, F₃,etc.) may be normalized by comparison against the heart rate frequency(F₁). Such normalized value may be determined as a ratio of themagnitudes and may be used as a blood volume metric to evaluate thehemodynamic state of the patient 102. Other similar blood volume metricsbased at least in part upon the frequency and magnitude values of theone or more harmonic frequencies (F₂, F₃, etc.) may be determined andused to evaluate the hemodynamic state of the patient 102 in variousembodiments.

Once patient status has been determined, the response unit 116 maydetermine whether a response is required and cause any required responseto be implemented (block 510). Additionally, or alternatively, theevaluation unit 118 or the response unit 116 may cause an indicator ofthe determined patient status to be stored or presented via the monitor120 (block 510). If the response unit 116 determines a response isrequired, the response unit 116 may further determine one or moreresponses that are appropriate to address the identified patient status.Such responses may include generating an alarm or other warning that thepatient status is abnormal, which may include information regarding thepatient condition. An alarm or warning may be presented via the monitor120 or may be communicated to another device for presentation. The alarmor warning may include a recommendation of one or more actions to takein response to the patient status. For example, the recommendation mayinclude an adjustment to a fluid therapy for the patient 102, which mayinclude a recommendation to administer one or more vasopressors orvasodilators. Such recommendation may be determined by the response unit116 as part of the required response. In some embodiments, this mayinclude sending an electronic communication to a user device (e.g., aworkstation or mobile device used by a physician, nurse, or technicianto monitor patient condition). In other embodiments, the alarm mayinclude an audible alarm or notification (e.g., via a speaker).

The responses may similarly include controlling the fluid source 110 toadjust fluid flow to the patient 102. The fluid source 110 may becontrolled to increase or reduce the rate of fluid flow to the patient102, including starting or stopping fluid flow. In some embodiments, theresponse may include controlling the fluid source 110 (or a deviceconnected thereto) to administer one or more drugs to the patient 102.For example, the fluid source 110 may be controlled to administer one ormore vasopressors or vasodilators in a fluid delivered to the peripheralvein 108 via the IV tube 104 and venous access device 106. Where thefluid source 110 includes a pump, the response may include controllingthe operation of the pump, such as by increasing or decreasing pumpspeed, flow rate, or mode of operation, as well as starting or stoppingthe pump. In some embodiments, the fluid source 110 may be controlled toadminister a quantity of a drug to the patient 102 via the fluid. Forexample, the fluid source 110 may be controlled to add a quantity of thedrug to the fluid. In some embodiments, the response may includecontrolling the rate of respirations associated with a ventilator and/oradministering a medicament, such as albuterol, via a nebulizer.

Additional embodiments of specific analysis and response methodsutilizing the PIVA system 100 are further described elsewhere herein ingreater detail.

Magnitude Ratio and Other Comparisons

In some embodiments, the patient status metric may be determined basedupon a comparison of magnitudes (P_(N) and P_(M)) associated withdifferent frequency peaks (F_(N) and F_(M)) based upon the sameplurality of data values (i.e., for the same evaluation window). Forexample, a ratio of the magnitudes associated with heart rate and firstharmonic frequencies F₁ and F₂ may be used to determine a hemodynamicmetric for the patient, such as a systemic vascular resistance or ablood volume status. Such ratios may be particularly useful innormalizing magnitudes associated with harmonic frequencies (F_(H)) toobtain more robust and more accurate patient status metrics. Similarly,ratios between magnitudes of the frequency-domain representation of thePVP signal associated with different harmonic frequencies (e.g., F₂ andF₃) may be used to determine hemodynamic state of the patient 102 (e.g.,blood volume status). In further embodiments, the patient status metricmay be determined based upon a comparison of magnitudes associated withthe same one or more frequencies (F_(N)) of peaks (P_(N)) determined fordifferent pluralities of data values (i.e., for different evaluationwindows). For example, analysis of a change in the absolute or relativemagnitude associated with heart rate frequency F₁ over time may be usedto determine a hemodynamic metric. Information regarding the patientstatus may be stored in a memory, presented to a user via the monitor120, or used by the response unit 116 to generate and implement aresponse (e.g., presenting an alarm or controlling the operation of thefluid source 110), including any of the responses discussed furtherbelow.

As mentioned above, a ratio of the magnitudes associated with frequencypeaks F₁ and F₂ may be used to determine systemic vascular resistance.However, other ways to determine systemic vascular resistance arecontemplated. For example, a change of one of the plurality of frequencypeaks (e.g., F₁) or a change of one of the plurality of frequency peaks(e.g., F₁) relative to another of the plurality of frequency peaks(e.g., F₂) may be used to determine systemic vascular resistance. Asanother example, a difference between any two of the respiratoryfrequency (F₀), the heart rate frequency (F₁), the first harmonicfrequency (F₂), and the second harmonic frequency (F₃) may be used todetermine systemic vascular resistance. As another example, a ratio ofany two of the respiratory frequency (F₀), the heart rate frequency(F₁), the first harmonic frequency (F₂), and the second harmonicfrequency (F₃) may be used to determine systemic vascular resistance. Ifthe determined systemic vascular resistance is abnormal, the fluidsource 110 can provide fluid therapy to increase or decrease thesystemic vascular resistance when the value is low or high,respectively. For example, when the response unit 116 generates andimplements a response (e.g., controlling the operation of the fluidsource 110), the systemic vascular resistance may be updated based atleast in part upon a change in frequency peak of at least one of therespiratory frequency (F₀), the heart rate frequency (F₁), the firstharmonic frequency (F₂), and the second harmonic frequency (F₃) inresponse to the fluid provided from the fluid source 110 to thecirculatory system of the patient via the IV tube 104. The changes infrequency peak(s) in response to fluids may be able to differentiatebetween regular (hemorrhagic) shock and distributive (septic) shock. Forinstance, if the frequency-domain representation of the PVP signal ofthe patient returns to normal after fluid therapy, the patient is mostlikely in regular shock due to fluid loss, but if the FFT signal doesnot return to normal after a period, the patient may be in indistributive shock. Other forms of therapy for adjusting the systemicvascular resistance are contemplated, such as vasopressin andvasodilator medications.

Distinguishing Respiratory Peaks from Cardiac Peaks

In certain instances, similarities shared by respiratory and pulse ratewaveforms pose risks of potential signal mis-identification,particularly when one or both of the respiratory signal or pulse ratesignal fluctuates in magnitude. The relative x-axis location of the P₀and P₁ peaks may be an unreliable reference for a practitioner todistinguish the respiratory signal from the pulse rate signal,particularly if a change in magnitude of one or both of the respiratoryor pulse rate signal (e.g., a fluctuation) occurs while thepractitioner's attention to the signal display was diverted.

As previously mentioned, an approach to interpreting signals on a PIVAdisplay is to assume that the lower frequency slower peak (F₀) is therespiratory peak, and the next-faster (higher frequency) peak (F₁)represents the heart rate. For example, with reference to FIG. 4B and aspreviously noted above, under ordinary conditions, the peak (P₀) withthe lowest frequency (F₀) corresponds to the respiration rate of thepatient 102, and the peak (P₁) with the next-lowest frequency (F₁)corresponds to the heart rate of the patient 102.

This approach is premised upon an assumption that the cardiac rate isalways faster than the respiratory rate. However, in certain (usuallyclinically catastrophic) situations, this assumption may not hold true.

For instance, there are clinical situations in which the lower frequencyslower peak is actually reflecting the heart rate and the next-fasterhigher frequency peak is actually reflecting the respiratory rate. Forexample, with reference to FIG. 4C, there are certain situations wherethe peak (P₁) with the lowest frequency (F₁) corresponds to the heartrate of the patient 102, and the peak (P₀) with the next-lowestfrequency (F₀) corresponds to the respiratory rate of the patient 102.For example, graphically, the respiratory peak (P₀) is to the right ofthe heart rate peak (P₁) on the x-axis in FIG. 4C. This situation may becommonly referred to as reversal of respiratory and cardiac peaks.

Furthermore, signal noise occurring coincidently near a typical heartrate could also make it difficult to distinguish a cardiac peak from arespiratory peak. Therefore, identifiers other than the expectedrespective x-axis locations of the F₀ and/or F₁ peaks based on typicalheart rates and/or respiratory rates would be helpful.

In particular embodiments, the PIVA system 100 utilizes additionalwaveforms and other information, in addition to the relative x-axislocation of the F₀ and F₁ peaks (which are typically the two lowestfrequency peaks), to increase the certainty of which waveformcorresponds to the pulse waveform, or at least more readily identifysituations in which the F₀ and F₁ peaks may not reliably represent therespiratory and pulse rate waveforms.

In an embodiment, and with reference to FIG. 4C, a method fordistinguishing respiratory peaks from cardiac peaks includes identifyinga substantially-repeating first peak frequency (F₀) associated withlocal maxima of the frequency-domain peripheral venous pressure signal.The method further includes identifying a substantially-repeating secondpeak frequency (F₁) associated with local maxima of the frequency-domainperipheral venous pressure signal, distinct from the identified firstpeak frequency. One of the first peak frequency (F₀) and second peakfrequency (F₁) is a respiratory signal and the other of the first peakfrequency (F₀) and second peak frequency (F₁) is a cardiac signal. Themethod further includes identifying at least a substantially-repeatingfirst harmonic (F₂). As will be determined, the substantially-repeatingfirst harmonic (F₂) is associated with one of the first peak frequency(F₀) or the second peak frequency (F₁).

In an embodiment, when there is an indication of a change in x-axislocation of either F₀ or F₁, the identification of the first or secondpeak frequency is confirmed by verifying the presence or absence of theassociated first harmonic (F₂). For example, because the location, alongthe x-axis, of the first harmonic peak is expected to be double thex-axis location for the heart rate signal peak x-axis location,verifying the presence or absence of the associated first harmonic (F₂)includes scanning for the presence of the associated first harmonic (F₂)at a location along an x-axis of a PIVA signal pattern that is doublethe value of an x-axis location of the one of the first peak frequencyor the second peak frequency. As used herein, double is intended toencompass exactly double as well as within ±15% of double.

In an alternate embodiment, the step of verifying the presence orabsence of the associated first harmonic may instead be performed by atrigger different from an indication in change in x-axis location ofeither F₀ or F₁. For instance, the verification step may be performedupon each iteration of the FFT calculation employed to generate theplotted PIVA signal.

The indication of a change in x-axis location of either the first orsecond peak frequencies (or a routine verification step performed uponeach FFT calculation) can include identification of an inversion inrelative amplitude of the first and second peak frequencies.

The method may further including identifying a substantially-repeatingsecond harmonic (F₃) associated with the same one of the first peakfrequency or the second peak frequency with which the identified firstharmonic F₂ is associated. Likewise, confirming the identification ofthe first or second peak frequency can further include verifying thepresence or absence of the associated second harmonic (F₃). For example,because the location, along the x-axis, of the second harmonic peak isexpected to be triple the x-axis location for the heart rate signal peakx-axis location, verifying the presence or absence of the associatedsecond harmonic (F₃) includes scanning for the presence of theassociated second harmonic (F₃) at a location along an x-axis of a PIVAsignal pattern that is triple the value of an x-axis location of the oneof the first peak frequency or the second peak frequency. As usedherein, triple is intended to encompass exactly triple as well as within±15% of triple.

In an embodiment, the mathematical relationship between x-axis locationsof F₁, F₂, and F₃ are used to confirm that the F₁ peak represents theheart rate (even though graphically, the respiratory peak (P₀) is to theright of the heart rate peak (P₁) on the x-axis). For example,regardless of the respiratory peak (P₀) and the heart rate peak (P₁)relative positions on the x-axis, it is determined that the heart ratepeak is ½ the distance from the associated first harmonic (F₂) and is ⅓the distance from the associated second harmonic (F₃), according to themathematical relationship identified above.

In a situation where the F₂ and F₃ peaks are either not found, or arenot found at their expected locations, this would be indicative of theF₁ peak possibly not representing the heart rate, and a practitionercould be alerted to the fact that an F₀/F₁ reversal may have occurred.

In an embodiment, the method disclosed above may be performed by any ofthe PIVA system 100, the PIVA device 130, and the integrated fluidsource 140.

Related Determination of Respiratory Metrics

In another embodiment, respiratory metrics may be determined, andtracked, from sensed pressure waveforms. For example, a respiratoryfrequency may be identified and evaluated to determine, among otherthings, risk of atelectasis, compliance with inspiratory spirometry, orrespiratory insufficiency in the patient.

FIG. 6 illustrates a block diagram of an exemplary PIVA system 600 foruse in measuring, analyzing, and responding to peripheral venous bloodpressure of a patient 602. The exemplary PIVA system 600 is, in manyways, similar to the PIVA system 100 described above. It should beappreciated that PIVA system 600 can perform the same methods,processes, analysis, and calculations as that of PIVA system 100. Forexample, the PIVA system 600 may measure a pressure signal associatedwith the patient's peripheral vein, analyze the pressure using PIVAtechniques to identify key frequency components of the pressure signal,and analyze the key frequency components of the pressure signal todetermine patient status based upon one or more metrics, as discussedbelow.

The PIVA system 600 includes an IV tube 604 in fluid connection with thecirculatory system of the patient 602. Specifically, a venous accessdevice 606 may be inserted into a peripheral vein 608 of the patient 602at an access point. The venous access device 606 may include a needle,catheter (such as a peripherally inserted central catheter), cannula, orother means of establishing a fluid connection between the IV tube 604and the peripheral vein 608. The venous access device 606 may be aseparate component connected to the IV tube 604 or may be formed as anintegral portion of the of the IV tube 604. In either case, the venousaccess device 606 may include a terminal end inserted into theperipheral vein 608 at the access point and a connecting end thatconnects to a primary portion of the IV tube 604. The primary portion ofthe IV tube 604 may serve as a conduit between the venous access device606 and a fluid source 610.

The fluid source 610 may include a fluid container and a flowcontroller. According to various embodiments, the flow controller mayinclude a pump, such as an infusion pump, a dialysis pump, and/or anyother medical fluid pump. The flow controller may also include any flowrestrictor capable of preventing or otherwise controlling the rate thatthe fluid flows out of the fluid contained. For example, the flowrestrictor may be a roller clamp, a valve, or any other device capableof being controlled to restrict the flow of the fluid. In someembodiments, the flow controller may be operated to adjust the flowrestrictor to permit fluid within the fluid container to flow into theIV tube 604 and/or adjust the rate that the fluid within the fluidcontainer flows into the IV tube 604.

At some point along the primary portion of the IV tube 604, a pressuresensor 612 may be disposed in fluid connection with the interior of theIV tube 604. The pressure sensor 612 is thus also in fluid connectionwith the peripheral vein 608 of the patient through the IV tube 604 andthe venous access device 606. The pressure sensor 612 is thereby enabledto measure pressure changes in the peripheral venous system of thepatient 602 based upon changes in the fluid pressure within the IV tube604. In other embodiments, the pressure sensor 612 may not be disposedin fluid connection with the interior of the IV tube 604. For example,the pressure sensor 612 may instead be attached to the exterior of theIV tube 604 and thereby disconnected from the fluid source 610. Asanother example, the pressure sensor 612 may be coupled to the IV tube604 via a flexible membrane that provides a sterile barrier between thefluids and the pressure sensor 612. The pressure sensor 612 may, in somesuch embodiments, measure pressure based upon acoustic or opticalphenomenon at the sensor location. In some embodiments, the pressuresensor 612 may be disposed at a terminating end (i.e., a capped off end)of an IV tube 604 inserted specifically for the purpose of measuringpressure within the peripheral vein 608, in a manner similar to thedevice illustrated above in FIG. 2. In still other embodiments, othersensors may be used instead of the pressure sensor 612, such as forcesensors, sound sensors, and sensors that need not be in fluid contactwith the peripheral vein 608 of the patient through the IV tube 604 andthe venous access device 606. In yet further embodiments, the sensor 612may be disposed within a portion of a needle, catheter, or other venousaccess device 606 that is inserted within the peripheral vein 608 of thepatient 606, such that PVP may be measured in situ within the peripheralvein 608. Such in situ measurement is advantageous inasmuch as itobviates the effect of variation in temperature, fluidviscosity/density, access device resistance, and other factors on theunmodified transmission of pressure waveforms within the IV tube 604.

In various embodiments, the pressure sensor 612 may be positioned atvarious distances from the access point of the peripheral vein 608, froma location within the peripheral vein 608 or a location proximate to theconnecting end of the venous access device 606 to a position proximateto the fluid source 610 or at a terminating end of the IV tube 604. Thepressure sensor 612 is illustrated as being at an intermediate locationalong the length of the IV tube 604 in order to illustrate better thevarious components of the PIVA system 600. In some embodiments, thepressure sensor 612 may directly measure fluid pressure within the IVtube 604. Specifically, the pressure sensor 612 may include a transducerthat provides an electronic pressure signal indicative of the pressuredetected by the transducer to an analysis component 614 via a connection622. The electronic pressure signal may be an analog electrical signaldirectly provided by the transducer or may be a preprocessed digitalsignal indicating pressure values based upon the transducer interfacewith the primary portion of the IV tube 604. In embodiments in which thepressure sensor 612 is not in fluid connection with the IV tube 604 orthe peripheral vein 608, the pressure sensor 612 may nonetheless includeone or more transducers to generate electronic signals associated withthe PVP. For example, the pressure sensor 612 may use one or moremicrophones disposed to detect sound at an exterior surface of an IVtube 604 to generate electronic pressure signals indicative of pressurewithin the IV tube 604 as a proxy for PVP within the peripheral vein608.

The analysis component 614 is communicatively connected to the pressuresensor 612 to receive the electronic pressure signal via the connection622. The analysis component 614 may include general-purpose orspecial-purpose processing hardware, such as microprocessors orspecial-purpose analysis circuits. As shown, the analysis component 614may include one or more units for performing the PIVA analysis. Aresponse unit 616 may identify and control responses based upon thepressure data from the pressure sensor 612. The response unit 616 maycontrol the presentation of alarms, the operation of the fluid source610, such as by controlling the rate of fluid flow, or the operation ofa ventilator 652, such as by controlling the rate of respiration. Todetermine appropriate responses, the response unit 616 may receiveevaluation data from an evaluation unit 618, which may include metricsdetermined from the electronic pressure signal. The evaluation unit 618may obtain pressure values (or signal values directly or indirectlyassociated with PVP) from the electronic pressure signal and evaluatethe pressure values to determine information regarding the patient 602,such as blood volume metrics, respiratory metrics, or other metrics asdescribed in further detail below. The information generated by theevaluation unit 618 may also be stored or presented for patientmonitoring. In alternative embodiments, additional, fewer, oralternative units may be included. For example, the evaluation unit 618may perform the functions ascribed to the response unit 616 herein. Asanother example, the analysis conducted by the analysis component 614may be performed at any point between the signal source, such as thepressure sensor 612, and a display unit, such as a monitor 620.

The analysis component 614 may be communicatively connected to themonitor 620 via a connection 626 in some embodiments. The monitor 620may be a separate monitor for displaying information regarding thepatient or may be incorporated into another device, such as a dialysispump, a patient-controlled analgesia pump, or an infusion or other pumpassociated with IV tube 604, or other flow controller of the fluidsource 610. The monitor 620 may also be communicatively connected to thefluid source 610 via a connection 628 to receive and display informationassociated with the fluid source 610. In some embodiments, the monitor620 may be used to control the operation of the fluid source 610, suchas by adjusting the flow controller to alter fluid flow rate, durationof operation, mode of operation, etc. In some embodiments, the monitor620 may also be communicatively connected to a ventilator control 650via a connection 629 to receive and display information associated withthe respirator 652. The ventilator control 650 may control the operationof the ventilator 652 via a connection 651. For example, the ventilatorcontrol 650 may control a rate of respiration, a volume of oxygen perrespiration, a respiratory pressure, etc. In some embodiments, themonitor 620 may be used to control the operation of additional oralternative respiratory equipment, including an extracorporeal bloodoxygenation unit (such as a continuous renal replacement therapy unit).The analysis component 614 may similarly be communicatively connected tothe fluid source 610 via connection 624 in some embodiments. Theanalysis component 614 may receive information regarding operation ofthe fluid source 610 for use in evaluating the patient by the evaluationunit 618. The response unit 616 may also communicate with the fluidsource 610 to control operation of the fluid source 610 and/or theventilator control 650 to control operation of the ventilator 652 inresponse to information regarding the patient determined based upon theelectronic pressure signal from the pressure sensor 612.

The various connections 622, 624, 626, 628, 629, and 651 may each bewired or wireless connections in various embodiments. Moreover, some orall of the connections 622, 624, 626, 628, 629, and 651 may be internalto devices, such as a PIVA device 630 or a PIVA-integrated fluid controldevice 640. The PIVA device 630 may incorporate the pressure sensor 612and analysis component 614 (along with associated connections) into adevice that may be attached to or within the IV tube 604 to perform PIVAmonitoring of the patient 602. The PIVA-integrated fluid control device640 may include a computer-controlled fluid reservoir (e.g., the fluidcontainer of the fluid source 610) and/or pump (e.g., the flowcontroller of the fluid source 610) configured to utilize PIVAmonitoring of the patient 602 in controlling the flow of fluids from thefluid container of the fluid source 610. Like the PIVA device 630, thePIVA-integrated fluid control device 640 may include the pressure sensor612 and analysis component 614, along with the fluid source 610 and themonitor 620 (along with associated connections). Alternative embodimentsmay include additional, fewer, or alternative components in alternativeconfigurations.

With reference to the PIVA system 600 described herein, and the methodsdisclosed above, respiratory status metrics may be readily determined.The respiratory status metrics may include metrics indicative of arespiratory volume/depth and/or a respiratory effort. As describedabove, respiratory depth may correlate to the magnitude of the peak (P₀)associated with the respiratory frequency (F₀). Accordingly, respiratoryvolume may correlate with the product of the magnitude of the peak (P₀),associated with the respiratory frequency (F₀), and the respiratoryfrequency (F₀). These values may be calculated via PIVA system 600.

The respiratory depth and/or volume metrics may be indicative of a riskof atelectasis, patient compliance with inspiratory spirometry,respiratory insufficiency, hyperventilation, and/or other respiratoryconditions. Additionally, the magnitude of the peak (P₀), associatedwith the respiratory frequency (F₀), may be associated with arespiratory effort metric.

In addition to the magnitudes of the peaks (P_(N)), the evaluation unit618 may also analyze the shape of the frequency-domain representation ofthe PVP signal at one or more of the frequencies (F_(N)) to determinethe one or more aspects of patient status. For example, the width of thelowest frequency peak (P₀) may be determinative of respiratoryconsistency. Generally speaking, consistent breathing patterns occur ata regular frequency. Accordingly, when the patient 602 exhibitsconsistent breathing patterns, the lowest frequency peak (P₀) containsfewer frequency variations. As such, when the lowest frequency peak (P₀)is narrow (e.g., a narrow parabolic peak), the evaluation unit 618 maydetermine that the patient 602 has a consistent breathing pattern.Conversely, when the patient 602 exhibits inconsistent breathingpatterns, there is generally higher variation the respiration frequency.Accordingly, the lowest frequency peak (P₀) for this patient will tendto be wider, incorporating the variance in the respiration rate. Thus,when the lowest frequency peak (P₀) is wide (e.g., a wide parabolicpeak), the evaluation unit 618 may determine that the patient 602 has aninconsistent breathing pattern. In order to calculate the width of thepeak, the evaluation unit 618 may use any generally known peak-widthcalculation techniques, such as, for example, a full-width half maximum(FWHM) width calculation.

In another aspect, the evaluation unit 618 may also analyze the slope ofthe either the rising-edge or falling-edge of the peaks (P_(N)) todetermine the one or more aspects of the patient status. For example,similar to the width of the lowest frequency peak (P₀), the slopes ofthe lowest frequency peak (P₀) may also indicate respiratoryconsistency. Generally, shallower slopes correspond to wider peaks.However, comparing the rising-edge slope and the falling-edge slope ofthe lowest frequency peak (P₀) may indicate additional aspects of thepatient status. To this end, when the respiratory rate of the patient602 speeds up, the lowest frequency peak (P₀) may begin to widen on thefalling-edge to incorporate the frequency content associated with thefaster respiratory rate. Thus, this quickening trend in breathingpattern may be detected by determining that the lowest frequency peak(P₀) has a shallower falling-edge slope as compared to the rising-edgeslope. Conversely, as the respiration rate of the patient 602 slowsdown, the lowest frequency peak (P₀) may shift such that the peakencompasses the lower respiration frequency content. Accordingly, thisslowing trend in breathing pattern may be detected by determining thatthe lowest frequency peak (P₀) has a steeper falling-edge slope ascompared to the rising-edge slope.

In still other aspects, a respiratory effort metric, such as work ofbreathing, may correlate to a ratio between the magnitude of the peak(P₀) corresponding to the respiratory frequency (F₀) to the magnitude ofthe peak (P₁) corresponding to the heart rate frequency (F₁).Additionally, a respiratory effort metric associated with the presenceof a respiratory obstruction may be determined by analyzing the shape ofthe peak (P₀) corresponding to the respiratory frequency (F₀). Theobstruction may either be an inspiratory obstruction, such as croup, orit may be an expiratory obstruction, such as asthma or chronicobstructive pulmonary disease.

It should be appreciated that while the pressure signal analysistechniques described herein have been generally described with respectto PIVA system 600, these pressure signal analysis techniques may beapplied to pressure signals detected by other systems. To this end, insome embodiments, the pressure sensor 612 may be located in alternativechannel of the circulatory system as compared to a peripheralintravenous channel. Such alternative channels include a central venouschannel, an arterial channel, as well as a peritoneal dialysis channel.As described above, some of these alternative channels are capable ofdetecting lower-than-respiratory frequencies, such as pressurefluctuations associated with gut behavior. Accordingly, as describedelsewhere herein, in these embodiments, the pressure sensor and/or adevice communicatively coupled to the pressure sensor may transmit tothe evaluation unit 618 a peak index corresponding to the respiratoryfrequency.

More generally, any of the systems disclosed herein, such as PIVA system100 and PIVA system 600 can perform any of the methods disclosed herein.

As used in this specification, including the claims, the term “and/or”is a conjunction that is either inclusive or exclusive. Accordingly, theterm “and/or” either signifies the presence of two or more things in agroup or signifies that one selection may be made from a group ofalternatives.

The many features and advantages of the present disclosure are apparentfrom the written description, and thus, the appended claims are intendedto cover all such features and advantages of the disclosure. Further,since numerous modifications and changes will readily occur to thoseskilled in the art, the present disclosure is not limited to the exactconstruction and operation as illustrated and described. Therefore, thedescribed embodiments should be taken as illustrative and notrestrictive, and the disclosure should not be limited to the detailsgiven herein but should be defined by the following claims and theirfull scope of equivalents, whether foreseeable or unforeseeable now orin the future.

The invention is claimed as follows:
 1. A blood volume evaluation systemconfigured for monitoring a patient using a measurement associated witha peripheral venous pressure (PVP) within a peripheral vein of acirculatory system of the patient, comprising: a PVP sensor including atransducer configured to be placed in fluid connection with theperipheral vein and configured to generate an electronic signalassociated with the PVP; and an evaluation unit, including a computerprocessor communicatively connected to the PVP sensor to receive theelectronic signal and a memory storing non-transitory computer-readableinstructions that, when executed by the computer processor, cause theevaluation unit to: obtain a time-domain PVP signal, including aplurality of values of the electronic signal over a sample period;decompose the time-domain PVP signal into frequency components; identifya plurality of frequencies, including a heart rate frequency (F₁) and aharmonic frequency (F_(H)) at a harmonic of the heart rate frequency(F₁), such that the harmonic frequency (F_(H)) is different from theheart rate frequency (F₁); and calculate a blood volume metric based atleast in part upon the heart rate frequency (F₁) and the harmonicfrequency (F_(H)).
 2. The blood volume evaluation system of claim 1,wherein the blood volume metric is an indication of one of thefollowing: hypovolemia, hypervolemia, or euvolemia.
 3. The blood volumeevaluation system of claim 1, further configured to present alarms to auser, wherein the instructions further cause the evaluation unit tocommunicate an alarm indicator to a presentation unit when the bloodvolume metric indicates the blood volume of the patient is abnormal, thealarm indicator causing the presentation unit to present an alarm. 4.The blood volume evaluation system of claim 3, wherein the alarmincludes a recommendation of an action to be taken in response to thedetermined blood volume metric.
 5. The blood volume evaluation system ofclaim 1, wherein the electronic signal is an electronic pressure signalindicative of pressure within an IV tube.
 6. The blood volume evaluationsystem of claim 5, wherein: the transducer of the PVP sensor is apressure sensor and is disposed in fluid connection with the interior ofthe IV tube; and the interior of the IV tube is configured to be placedin fluid connection with the circulatory system of the patient via theperipheral vein.
 7. A device configured for measuring and evaluatingblood volume of a patient, comprising: a peripheral venous pressure(PVP) sensor, including a transducer configured to be placed in fluidcommunication with a peripheral vein to generate an electronic signalassociated with a pressure within the peripheral vein of a circulatorysystem of the patient; and an evaluation unit, including a computerprocessor communicatively connected to the PVP sensor to receive theelectronic signal and a memory storing non-transitory computer-readableinstructions that, when executed by the computer processor, cause theevaluation unit to: obtain a time-domain PVP signal, including aplurality of values of the electronic signal over a sample period;decompose the time-domain PVP signal into frequency components; identifya plurality of frequencies, including a heart rate frequency (F₁) and aharmonic frequency (F_(H)) at a harmonic of the heart rate frequency(F₁), such that the harmonic frequency (F_(H)) is different from theheart rate frequency (F₁); and calculate a blood volume metric based atleast in part upon the heart rate frequency (F₁) and the harmonicfrequency (F_(H)).
 8. The device of claim 7, wherein the blood volumemetric is an indication of one of the following: hypovolemia,hypervolemia, or euvolemia.
 9. The device of claim 7, wherein: obtainingthe time-domain PVP signal includes receiving and storing the pluralityof values of the electronic signal over the sample period.
 10. Thedevice of claim 7, wherein the sample period is a fixed duration that iscontinuously updated on a rolling basis as new values of the electronicsignal are obtained.
 11. The device of claim 7, wherein thetransformation is a fast Fourier transformation.
 12. The device of claim7, wherein the blood volume metric is further determined at least inpart based upon at least one or more additional harmonic frequencies ofthe heart rate frequency (F₁).
 13. The device of claim 7, wherein theblood volume metric is determined based at least in part upon anincrease or decrease in a magnitude associated with the harmonicfrequency (F_(H)).
 14. A method configured for measuring and evaluatingblood volume of a patient using a measurement associated with aperipheral venous pressure (PVP) within a peripheral vein of acirculatory system of the patient, comprising: monitoring, by atransducer of a PVP sensor configured to be placed in fluidcommunication with the peripheral vein, a physical phenomenon associatedwith the PVP within the peripheral vein of the circulatory system of thepatient; generating, by the PVP sensor, an electronic signal associatedwith the PVP over a sample period, the values of the electronic signalover the sample period forming a time-domain PVP signal; decomposing, bya processor of an evaluation unit, the time-domain PVP signal intofrequency components; identifying, by the processor of the evaluationunit, a plurality of frequencies, including a heart rate frequency (F₁)and a harmonic frequency (F_(H)) of the heart rate frequency (F₁), suchthat the harmonic frequency (F_(H)) is different from the heart ratefrequency (F₁); and calculating, by the processor of the evaluationunit, a blood volume metric based at least in part upon the heart ratefrequency (F₁) and the harmonic frequency (F_(H)).
 15. The method ofclaim 14, wherein the blood volume metric is an indication of one of thefollowing: hypovolemia, hypervolemia, or euvolemia.
 16. The method ofclaim 14, wherein calculating the instantaneous blood volume metricbased at least in part upon the heart rate frequency (F₁), a firstharmonic frequency (F₂), and a second harmonic frequency (F₃) includesthe equation${{PIVA}\mspace{14mu}{Score}} = {{c_{3}{\tanh( \frac{g_{0} + {g_{1}{mag}^{f\; 1}} + {g_{2}{mag}^{f\; 2}} + {g_{3}{mag}^{f\; 3}}}{2} )}} + {c_{2}{\tanh( \frac{h_{0} + {h_{1}{mag}^{f\; 1}} + {h_{2}{mag}^{f\; 2}} + {h_{3}{mag}^{f\; 3}}}{2} )}} + {c_{1}{\tanh( \frac{i_{0} + {i_{1}{mag}^{f\; 1}} + {i_{2}{mag}^{f\; 2}} + {i_{3}{mag}^{f\; 3}}}{2} )}} + c_{0}}$wherein each of c₀, c₁, c₂, c₃, g₀, g₁, g₂, g₃, h₀, h₁, h₂, h₃, i₀, i₁,i₂, and i₃ are constants, wherein mag^(f1) is the magnitude of the heartrate frequency (F₁), wherein mag^(f2) is the magnitude of the firstharmonic frequency (F₂), and wherein mag^(f3) is the magnitude of thesecond harmonic frequency (F₃).
 17. The method of claim 14, wherein theplurality of frequencies further include one or more additional harmonicfrequencies associated of the heart rate frequency (F₁).
 18. The methodof claim 17, wherein the one or more additional harmonic frequencies areidentified as the frequencies associated nearest to integer multiples ofthe heart rate frequency (F₁).
 19. The method of claim 18, the bloodvolume metric is further determined at least in part based upon at leastone of the additional harmonic frequencies.
 20. The method of claim 19,wherein the blood volume metric is determined based at least in partupon a harmonics ratio between the harmonic frequency (F_(H)) and the atleast one of the additional harmonic frequencies.